This is knee cartilage and not growth plate cartilage but some characteristics may apply.

Michael mentioned Nerve Growth Factor before in a supplement review.

Rac1 mediates load-driven attenuation of mRNA expression of nerve growth factor beta in cartilage and chondrocytes.

“To determine effect of gentle loads applied to the knee on mRNA expression of nerve growth factor, particularly, the active beta subunit (NGFβ) in cartilage and chondrocyte.  Cyclic compressive loads in vivo and fluid flow in vitro were used to determine the mRNA levels. Alteration of Rac1 GTPase as well as effect of salubrinal, a specific inhibitor of eIF2α phosphatase was assessed. Knee loading at 1 N reduced mRNA levels of NGFβ and its low affinity receptor, p75 in cartilage and subchondral bone{This is in contrast to the Zenith Height product which states that NGFB would increase height}. In cartilage, knee loading at 1 N reduced the phosphorylation level of p38 MAPK (p38-p) and activity of Rac1 GTPase. Consistent with in vivo results, fluid flow at 5 and 10 dyn/cm(2) reduced mRNA levels of NGFβ and p75 in C28/I2 human chondrocytes. SB203580, which decreases p38-p, reduced the mRNA levels of NGFβ and p75. Silencing Rac1 by siRNA decreased the levels of p38-p and NGFβ mRNA but not p75. Furthermore, administration of salubrinal reduced FRET-based activity of Rac1 as well as the mRNA levels of NGFβ and p75.”

The authors interest in NGFB is NGFB’s role in causing pain in cartilage.

“the activation of the p75 receptor has been shown to promote neuronal cell death”

“A basal expression level of NGFβ is high in embryos undergoing skeletal morphogenesis and low in mature cartilage.”<-Maybe NGFB is responsible for growing pains?  This would also suggest that NGFB may be positive for height growth.  It’s also possible that NGFB is just a correlation for height growth and not a causal factor.

12 week old mice were used.  Durating of 1 or 3 hours of LSJL was used used and 1 or 3N was used.  In other LSJL studies, typically 0.5N were used for the force but in one study 1N was used.

“lateral loads to the knee were applied for 5 min at 5 Hz with a peak-to-peak force of 1 and 3 N.”

Levels of NGFB were higher for 3 hours than 1 hour but both were lower than control(see figure 1 in linked study).

Loading at 3N increased p38 phosphorylation whereas loading at 1N decreased p38 phosphorylation levels.  Suppressing p38-p levels may increase chondrocyte proliferation whereas increasing p38-p levels may favor differentiation.  p38 has been implicated in chondroinduction and increasing Sox9 levels.

Fluid Flow of 5 dyn per cm^2 decreased p38-phosphorylation wereas other levels 2, 10, and 20 increased it.

“Knee loading induces not only pressure alterations but also pressure driven fluid flow to chondrocytes. Unlike well-studied effects of normal stress on chondrocytes, it has been recently suggested that a consequence of compressive loading is production of hydrostatic pressure as well as fluid flow to cartilage. In osteoarthritis, chondrocytes are exposed to flow shear due primarily to synovial fluid and high amplitude of fluid flow reproduces the hallmarks of osteoarthritis in vitro”

This was admittedly a dissapointing LSJL study but based on how NGF-Beta affects height we can see that there may be a need to use heavier LSJL loads.  Since p38-phosphorylation favors differentiation and heavier loads increased p38-phosphorylation more than medium loads.  Heavy loads may be needed to induce chondro-growth plate induction by LSJL.

Here’s an hypoxia study that may provide insight on p38 and chondroinduction:

Hypoxia promotes chondrogenesis in rat mesenchymal stem cells: a role for AKT and hypoxia-inducible factor (HIF)-1alpha.

“Cartilage is an avascular tissue and thus resides in a microenvironment with reduced oxygen tension. The aim of this study was to examine the effect of a low oxygen environment on MSC differentiation along the chondrogenic route. In MSCs exposed to chondrogenic growth factors, transforming growth factor-beta and dexamethasone, in a hypoxic environment (2% oxygen), the induction of collagen II expression and proteoglygan deposition was significantly greater than that observed when cells were exposed to the chondrogenic growth factors under normoxic (20% oxygen) conditions. The transcription factor, hypoxia-inducible factor-1alpha (HIF-1alpha), is a crucial mediator of the cellular response to hypoxia. Following exposure of MSCs to hypoxia (2% oxygen), HIF-1alpha translocated from the cytosol to the nucleus and bound to its target DNA consensus sequence. Similarly, hypoxia evoked an increase in phosphorylation of both AKT and p38 mitogen activated protein kinase, upstream of HIF-1alpha activation. Furthermore, the PI3 kinase/AKT inhibitor, LY294002, and p38 inhibitor, SB 203580, prevented the hypoxia-mediated stabilisation of HIF-1alpha. To assess the role of HIF-1alpha in the hypoxia-induced increase in chondrogenesis, we employed an siRNA knockdown approach. In cells exposed to HIF-1alpha siRNA, the hypoxia-induced enhancement of chondrogenesis, as evidenced by upregulation of collagen II, sox-9 and proteoglycan deposition, was absent. This provides evidence for HIF-1alpha being a key mediator of the beneficial effect of a low oxygen environment on chondrogenesis.”

The paper mentions ultrasound as being able to stabilize HIF-1.

“rat MSCs undergo chondrogenesis, as evidence by enhanced collagen II expression and proteoglycan deposition, when exposed to TGFβ and dexamethasone in a normoxic environment. When the MSCs were exposed the chondrogenic factors for 2 weeks in normoxia, followed by 1 week in hypoxia (2% oxygen), chondrogenesis was significantly enhanced, demonstrating that a reduced oxygen tension favours differentiation along the chondrogenic route. The hypoxic environment increased HIF-1α nuclear accumulation and its transactivation in an Akt- and p38-dependent manner. ”

“In ATDC5 chondroprogenitor, hypoxia alone favours chondrogenesis, whilst insulin-mediated chondrogenesis is inhibited by hypoxia ”

Thus it is more likely that heavier loads would be beneficial in an LSJL regime due to the effects of p38 phosphorylation.  However, in the LSJL gene expression study and several LSJL lengthening studies 0.5N was used.  Perhaps, the LSJL based lengthening does not involve p38 but rather the ERK pathway.  Sox9 was in fact upregulated in that study while a decrease in p38 phosphorylation tends to decrease Sox9 expression.